The goal of our activity is to understand the functional role and substrates underlying plastic changes in the human central nervous system and develop novel therapeutic approaches for recovery of function. Most of our work has focused on the study of plastic changes in the human motor, somatosensory and visual systems. This year, we identified behavioralgains in tactile discriminative skills in one hand associated with deafferentation in the other hand. In the visual domain, we found that light deprivation is associated with an increase in excitability of the visual cortex and a decrease in GABA levels in that region. This finding demonstrates the possibility of online monitoring minute to minute of changes in cortical GABA in behaving humans using magnetic resonance spectroscopy. In relation to use- dependent plasticity in motor cortex, we discovered that it is possible to modulate plasticity in one body part representation by stimulation with TMS and by stimulation of adjacent body part representations. We also developed two strategies to enhance use-dependent plasticity: by administration of d-amphetamine and also by concomitant administration of transacranial magnetic stimulation. In a collaborative effort with German investigators, we found that representational plasticity in somatosensory and motor cortex is more prominent in patients with phantom limb pain than in amputees without pain. In the area of rehabilitation after chronic stroke, we found that a rehabilitation treatment called "constraint induced therapy" appears to enhance the amount of use of the paretic arm long time after stroke. We have advanced in the understanding of the involvement of the intact hemisphere and nonprimary motor areas (particularly dorsal premotor cortex) in recovery of motor function after stroke. Our future goals are to improve our understanding of the functional role and substrates underlying plasticity of function in humans. On the basis of this understanding, we are starting to design and test interventions to improve motor disability after human diseases.